Indolent Systemic Mastocytosis, Smoldering Systemic Mastocytosis
Conditions
Keywords
ISM, SSM
Brief summary
This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + symptom directed therapy (SDT) with placebo + SDT in participants with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by SDT. Parts 1 and 2 will enroll participants with ISM. Participants enrolled in Part 2 will roll over onto Part 3 to receive treatment with elenestinib in an open-label fashion following completion of the earlier Part. Part K will enroll participants with ISM who have previously received an approved selective KIT inhibitor. The study also includes pharmacokinetic (PK) groups that will enroll participants with ISM.
Interventions
DRUGElenestinib
Elenestinib oral tablet
DRUGPlacebo
Placebo oral tablet
Sponsors
Blueprint Medicines Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part 1 and Part 2: Randomized, Blinded Part 3, Part K, Part S and PK groups: Non-randomized, Open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: All Participants: -Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2. Part 1 and PK groups: * Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review * Participant must have failed to achieve adequate symptom control for 1 or more Baseline symptoms, as determined by the Investigator, with at least 2 of the following symptom-directed therapies administered: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab. * Participants must have SDT for ISM symptom management stabilized for at least 14 days prior to starting screening procedures. * For participants receiving corticosteroids, the dose must be ≤ 20 mg/day prednisone or equivalent, and the dose must be stable for ≥ 14 days. Part K: -Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review Part S: -Participant has confirmed diagnosis of SSM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings by WHO diagnostic criteria. Part 2: -Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review Key
Exclusion criteria
* Participant has been diagnosed with any of the following WHO systemic mastocytosis (SM) sub-classifications: cutaneous mastocytosis only, SM with an associated hematologic neoplasm of non-MC lineage (SM-AHN), aggressive SM, mast cell leukemia, or mast cell sarcoma. * Participant has been diagnosed with another myeloproliferative disorder. * Participant has organ damage attributable to SM. * Participant has clinically significant, uncontrolled, cardiovascular disease * Participant has a QT interval corrected using Fridericia's formula (QTcF) \> \> 470 milliseconds (msec) (for females) or \> 450 msec (for males). * Participant has a history of a primary malignancy that has been diagnosed or required therapy within 3 years. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site. * Time since any cytoreductive therapy including masitinib and midostaurin should be at least 5 half-lives or 14 days (whichever is longer), and for cladribine, interferon alpha, pegylated interferon, or antibody therapy \< 28 days or 5 half-lives of the drug (whichever is longer), before beginning the screening period. * Participant has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy \< 14 days before beginning the screening period. Other protocol-defined criteria apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs) | Up to 12 weeks |
| Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS) | Baseline, Week 13 |
| Part 2: Mean change from baseline in ISM-SAF TSS | Baseline, Week 49 |
| Part 3: Number of participants with Adverse Events (AEs) | Up to 5 years |
| Part 3: Change from baseline in ISM-SAF TSS | Baseline up to 5 years |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: Change from baseline in serum tryptase | Baseline, Week 13 |
| Part 1: Change from baseline in KIT D816V allele fraction in blood | Baseline, Week 13 |
| Part 1: Change from baseline in Bone Marrow (BM) mast cells | Baseline, Week 13 |
| Part 1: Mean change from baseline in ISM-SAF individual symptom scores | Baseline, Week 13 |
| Part 1: Time to achieve 30% reduction from baseline in ISM-SAF TSS | Baseline up to Week 13 |
| Part 1: Time to achieve 30% reduction from baseline in ISM-SAF domain scores | Baseline up to Week 13 |
| Part 2: Proportion of participants achieving normalized tryptase | Baseline up to Week 49 |
| Part 2: Proportion of participants who achieve an undetectable level or at least a 50% reduction in KIT D816V Variant Allele Frequency (VAF) | Baseline up to Week 49 |
| Part 2: Proportion of participants achieving symptom control as defined by achieving mild symptoms | Baseline up to Week 49 |
| Part 2: Mean percent change from baseline in Bone Mineral Density (BMD) | Baseline, Week 49 |
| Part 2: Mean change from baseline in the annualized rate of anaphylaxis events | Baseline, Weeks 25 to 48 |
| Part 2: Mean change from baseline in Quality of Life (QoL) scores | Baseline, Week 49 |
| Part 2: Mean change from baseline in ISM-SAF domain scores | Baseline, Week 49 |
| Part 2: Number of participants with AEs | Up to Week 49 |
| Part 2: Proportion of participants with a 50% reduction in ISM-SAF TSS | Baseline, Weeks 24 and 48 |
| Part 2: Proportion of participants with a 50% reduction in ISM-SAF domain scores | Baseline, Weeks 24 and 48 |
| Part 2: Proportion of participants with a 30% reduction in ISM-SAF TSS | Baseline, Weeks 24 and 48 |
| Part 2: Proportion of participants with a 30% reduction in ISM-SAF domain scores | Baseline, Weeks 24 and 48 |
| Part 3: Proportion of participants achieving symptom control as defined by achieving mild symptoms | Baseline up to 5 years |
| Part 3: Change from baseline in ISM-SAF domain scores | Baseline, up to 5 years |
| Part 3: Proportion of participants achieving a normalized tryptase | Baseline up to 5 years |
| Part 3: Change from baseline in BMD | Baseline up to 5 years |
| Part 3: Change from baseline in the annualized rate of anaphylaxis events | Baseline up to 5 years |
| Parts 2 and 3: Change from baseline in serum tryptase | Baseline up to 5 years |
| Parts 2 and 3: Change from baseline in KIT D816V allele fraction in blood | Baseline up to 5 years |
| Parts 2 and 3: Change from baseline in Bone Marrow (BM) mast cells | Baseline up to 5 years |
| Parts 2 and 3: Proportion of participants achieving controlled disease | Baseline up to 5 years |
| Parts 2 and 3: Change from baseline in skin lesions as assessed by the fractional body surface area of the most affected skin area | Baseline up to 5 years |
| Parts 2 and 3: Change from baseline in the number of concomitant medications identified as SDT | Baseline up to 5 years |
| Parts 2 and 3: Change from baseline in ISM-SAF Individual Symptom Scores | Baseline up to 5 years |
| Parts 2 and 3: Change from baseline in ISM-SAF Lead (most severe) Symptom Score | Baseline up to 5 years |
| Parts 2 and 3: Change from baseline in QoL scores | Baseline up to 5 years |
| Part S: Number of participants with AEs | Baseline up to 5 years |
| Part S: Proportion of participants who achieve a Pure Pathologic Response (PPR) | Baseline up to 5 years |
| Part S: Mean change from baseline in ISM-SAF | Baseline, Week 25 |
| Part K: Number of participants with AEs | Baseline up to 5 years |
| Part K: Change from baseline in serum tryptase | Baseline up to 5 years |
| Part K: Change from baseline in KIT D816V allele fraction in blood | Baseline up to 5 years |
| Part K: Mean change from baseline in ISM-SAF TSS | Baseline up to 5 years |
| Part K: Change from baseline in QoL scores | Baseline up to 5 years |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Colombia, Czechia, France, Germany, Greece, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTBlueprint Medicines
Outcome results
None listed